Promoter Methylation of DNA Repair Genes Predicts Disease-free Survival of Gastric Adenocarcinoma after Adjuvant Radiotherapy

• Main Authors: Ning An, Zhuang Yu, Xin-Jia He, Yuan-Yuan Zhao, Li Yu, Yong-Chun Zhang, Hai-Jun Lu, Xue Yang
• Format: Article
• Language: English
• Published: Elsevier 2020-09-01
• Series: Molecular Therapy: Oncolytics
• Subjects: gastric adenocarcinoma; promoter methylation; adjuvant radiotherapy; disease-free survival
• Online Access: http://www.sciencedirect.com/science/article/pii/S2372770520300851

The relentless debate on postoperative adjuvant radiotherapy in gastric adenocarcinoma (GA) has been lasting for decades. In this study, a new biomarker, named promoter methylation burden of DNA repair genes (RPMB), was established to identify the subgroup of patients who might benefit from adjuvant radiotherapy. Methylation profiles of 397 GA tumor samples were downloaded from The Cancer Genome Atlas (TCGA). RPMB for a patient was defined as the ratio of methylated DNA repair genes to the number of all DNA repair genes. Subgroup analyses in term of overall survival (OS) and disease-free survival (DFS) indicated that most of the subgroups favored the high-RMPB group. Kaplan-Meier analysis showed that overall the patients with high RPMB after R0 resection had a significantly better clinical outcome regarding DFS (hazard ratio [HR] = 0.013, p = 0.042). Additionally, high-RPMB patients, who underwent adjuvant radiotherapy with both ≥T2 tumor and positive lymph nodes, showed superior DFS in comparison with the low-RPMB group (HR = 5.35 × 10−10, n = 26, p = 0.010). RPMB might be considered as a promising biomarker for decision-making with regard to postoperative adjuvant radiotherapy for GA patients.